Antipsychotic medication and prefrontal cortex activation: A review of neuroimaging findings

Edith J. Liemburg*, Henderikus Knegtering, Hans C. Klein, Rudie Kortekaas, Andre Aleman

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

32 Citations (Scopus)

Abstract

Decreased prefrontal activation (hypofrontality) in schizophrenia is thought to underlie negative symptoms and cognitive impairments, and may contribute to poor social outcome. Hypofrontality does not always improve during treatment with antipsychotics. We hypothesized that antipsychotics, which share antagonism at dopamine receptors, with a relatively low dopamine receptor affinity and high serotonin receptor affinity may have a sparing effect on prefrontal function compared to strong dopamine receptor antagonists. We systematically investigated the relation between serotonin and dopamine antagonism of antipsychotics and prefrontal functioning by reviewing neuroimaging studies. The weight of the evidence was consistent with our hypothesis that antipsychotics with low dopaminergic receptor affinity and moderate to high serotonergic affinity were associated with higher activation of the prefrontal cortex. However, clozapine, a weak dopamine and strong serotonin antagonist, was associated with decrease in prefrontal activation. Future studies should further elucidate the link between prefrontal activation and negative symptoms using prospective designs and advanced neuroimaging techniques, which may ultimately benefit the development of treatments for disabling negative symptoms. (C) 2011 Elsevier B.V. and ECNP. All rights reserved.

Original languageEnglish
Pages (from-to)387-400
Number of pages14
JournalEuropean Neuropsychopharmacology
Volume22
Issue number6
DOIs
Publication statusPublished - Jun-2012

Keywords

  • Antipsychotic agents
  • Prefrontal cortex
  • Monoamines
  • Negative symptoms
  • Neuroimaging
  • Schizophrenia
  • CEREBRAL-BLOOD-FLOW
  • NAIVE SCHIZOPHRENIC-PATIENTS
  • DISTRIBUTED NEURAL CIRCUITRY
  • WORKING-MEMORY DYSFUNCTION
  • ANTERIOR CINGULATE CORTEX
  • VAL(108/158) MET GENOTYPE
  • CARD-SORTING-TEST
  • 1ST-EPISODE SCHIZOPHRENIA
  • N-DESMETHYLCLOZAPINE
  • PHYSIOLOGICAL DYSFUNCTION

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